Biology subjects

Mosqueda, N.

Publications and source records attributed to Mosqueda, N..

3 recordsLinked to original sources

bioRxiv2025

A Role for Importin α in Ciliogenesis and Cilia Length Regulation during Nephrogenesis

Cilia are evolutionary conserved microtubule-based organelles involved in many biological processes. Motile cilia facilitate fluid flow, while primary cilia transduce developmental and growth signals. Defects in cilia structure or function can lead to a spectrum of ciliopathies. Ciliogenesis and length regulation depend on protein transport to the ciliary base, but the molecular mechanisms remain unclear. We demonstrate that the nuclear transport protein, importin , when membrane-localized via palmitoylation, or non-palmitoylated in the cytoplasm, localizes to the base or lumen of primary and motile cilia. There we find it is required to initiate ciliogenesis and maintain proper cilia length. We found importin binds Cep164, Cep78, and Arl13b, proteins essential for ciliogenesis and length maintenance. Disrupting importin palmitoylation in Xenopus laevis lead to abnormal kidney morphology and reduced renal primary cilia. These findings reveal a novel pathway through which importin contributes to ciliogenesis and advance understanding of ciliopathy etiology.

cell biology↗

bioRxiv2024

Presynaptic Nrxn3 is essential for ribbon-synapse assembly in hair cells

Hair cells of the inner ear rely on specialized ribbon synapses to transmit sensory information to the central nervous system. The molecules required to assemble these synapses are not fully understood. We show that Nrxn3, a presynaptic adhesion molecule, is critical for ribbon-synapse assembly in hair cells. In both mouse and zebrafish models, loss of Nrxn3 results in significantly fewer intact ribbon synapses. In zebrafish we demonstrate that a 60% loss of synapses in nrxn3 mutants dramatically reduces both presynaptic responses in hair cells and postsynaptic responses in afferent neurons. Despite a reduction in synapse function in this model, we find no deficits in the acoustic startle response, a behavior reliant on these synapses. Overall, this work demonstrates that Nrxn3 is a critical and conserved molecule required to assemble ribbon synapses. Understanding how ribbon synapses assemble is a key step towards generating novel therapies to treat forms of age-related and noise-induced hearing loss that occur due to loss of ribbon synapses. Summary StatementHearing and balance depend on specialized ribbon synapses that transmit sensory stimuli between hair cells and afferent neurons. We identify Nrxn3 as a key molecular player in ribbon-synapse assembly in hair cells.

neuroscience↗

bioRxiv2019

Retrograde mitochondrial transport is essential for mitochondrial homeostasis in neurons

Mitochondrial transport in neurons is essential for forming and maintaining axonal projections. While much is known about anterograde mitochondrial movement, the function of retrograde mitochondrial motility in neurons was unknown. We investigated the dynamics and utility of retrograde mitochondrial transport. Using long-term tracking of mitochondria in vivo, we found mitochondria in axon terminals turnover within hours via retrograde transport. Mitochondria do not return to the cell body solely for degradation; rather, mitochondria use bidirectional transport to redistribute themselves throughout the neuron. Disruption of retrograde mitochondrial transport severely depletes the cell body of mitochondria and impacts mitochondrial health throughout the cell. Altered mitochondrial health correlates with decreased synaptic activity. Using proteomics, we provide evidence that retrograde mitochondrial movement functions to maintain the organelles proteome. Together, our work demonstrates that mitochondrial retrograde transport is essential for the maintenance of a homeostatic population of mitochondria in neurons and consequently effective synaptic activity through promoting mitochondrial protein turnover.

neuroscience↗